DESCRIPTION The protochordate, Botryllus schlosseri, undergoes a genetically defined, natural transplantation reaction the edges of two growing colonies interact. This allorecognition phenomena is analogous to that seen in hematopoietic resistance (Hh) in the higher vertebrates: it is principally controlled by a single locus with multiple co-dominantly expressed alleles (called the Fu/HC); and it is likely the recognition of self which prevents a rejection reaction. Protochordates are phylogenetic predecessors to all chordates, thus the Fu/HC-based allorecognition system may either be the ancestral MHC, or possibly a novel allorecognition system still undiscovered in the vertebrates. However, the Fu/HC locus has never been characterized at the molecular level. Using Fu/HC defined, inbred strains of Botryllus developed in our lab, we are taking a genomic approach to isolate and analyze this locus by making a genetic map, isolating tightly-linked flanking markers, and using these to positionally clone the Fu/HC locus. Candidate genes will be correlated with functional histocompability and the corresponding polypeptides will be characterized.